The invention relates to treating cancer or benign tumors and, more particularly, to a method for treatment, or reducing the incidence of recurrence, of skin cancer or tumors comprising administration of a vaccine, including local administration of the vaccine as a therapeutic agent.
Skin cancer consists of three main types, namely, basal-cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma, and is the most common form of cancer globally. Understandably, there have been ongoing studies for many years searching for effective methods to treat, and possibly cure, these types of skin cancer.
It is generally accepted that human papillomavirus (HPV) is associated with causing certain types of skin cancer, particularly squamous cell carcinoma (SCC). HPV is a DNA virus that can infect certain types of tissues in humans. There are upwards of thirty subtypes of HPV and some of these subtypes have been associated with cervical cancer, including HPV16 and HPV18. HPV is not known to be a cause or to be associated with basal cell carcinoma (BCC) or melanoma.
Vaccines have been developed and shown to prevent cervical cancer in women and other conditions caused by or associated with HPV infection. GARDASIL® is a commercially available vaccine having activity against HPV (types 6, 11, 16, and 18).
GARDASIL® 9 is another commercially available vaccine marketed for prevention of HPV (types 16, 18, 31, 33, 45, 52, and 58). GARDASIL® is indicated for use in girls and boys from ages 9-26; GARDASIL® 9 is also indicated for use in girls from ages 9-26, and in boys from ages 9-15.
Other vaccines have been produced, as well, for treating subtypes of HPV, particularly HPV16 and HPV18. GARDASIL® and other known vaccines administered prophylactically, to prevent certain HPV infections and associated cancers, are referred to herein as “preventive vaccines.” These preventive vaccines are typically administered for systemic action, being injected into a patient subcutaneously or intramuscularly (e.g., deltoid), remote from any particular target, such as the cervix. Moreover, they are generally accepted to be effective prior to exposure to HPV and are not commonly known to be effective for treatment after exposure to, or infection with, HPV.
Other preventive vaccines include, for example, an improved vaccine composition as described in Chinese Pat App. No. 101890160 (CN '160) comprising certain L1 proteins of HPV (as in GARDASIL®), and additional HPV-specific components. Preventive vaccines comprising HPV-type 16 and 18 proteins are also suggested to provide cross-protection against other HPV types, as described in US Pub. No. 2005/0287161.
Vaccines used for treatment (referred to herein as “therapeutic vaccines”) are described. However, these therapeutic vaccines require more than viral-specific components, such as HPV L1 proteins that comprise the commercially available preventive vaccines, such as GARDASIL®.
US Pub. No. 2007/0218074 describes the use of a vaccine composition comprising host-cell peptides from an HPV-infected cell. The host-cell peptides, e.g., the early antigens, E6 or E7, that present on the surface of cells infected with HPV, are fragments of host-cell proteins. The criticality of the polypeptides E6 or E7 in a vaccine used in treating certain cancer types is described in Development of HPV vaccines for HPV-associated head and neck squamous cell Carcinoma, Devaraj, et al., Crit Rev Oral Biol Med. 2003; 14(5):345-62. Another vaccine which includes a host-cell protein (BAX) is described in U.S. Pat. No. 8,399,610.
Yet another vaccine composition comprising other or additional antigens in combination with HPV-16 peptides, is a vaccine composition described in US Pub. No. 2011/0070252 which additionally requires Trojan antigen.
US Pub. No. 2011/0110979 (U.S. '979) and US Pub. No. 2012/0288538 (U.S. '538) disclose therapeutic use of an HPV vaccine comprising E6 or E7 polypeptides (peptide fragments from host cells infected with HPV). U.S. '538 describes that E6 and E7 are crucial to induce transformation into HPV-infected cells, and states that a vaccine composition which does not include E6 or E7 would not be expected to work on cells that do not have E6 or E7, i.e., cells such as BCC that are not infected with HPV. The method described in the U.S. '979 publication additionally requires an immunostimulant or adjuvant.
Although the U.S. '979 and U.S. '538 publications describe the use of therapeutic vaccines against skin cancers, such as SCC or epithelial SCC, they do not describe use of the vaccine against other skin cancers, such as BCC or melanoma, likely based on the understanding that BCC and melanoma are not associated with HPV infection.
To the knowledge of the inventor, administration of HPV vaccines comprising only HPV antigens (being free of host-cell peptides), to a previously unimmunized patient, or an adult patient aged 27 or greater, to eliminate or reduce the incidence of recurrence of cancer, benign tumor or other skin lesion, has not been previously described. Nor has the direct or local injection of a vaccine to eliminate the lesion and reduce the incidence of its recurrence been previously described.
The limitations and disadvantages of the above uses of vaccines can be overcome by the use of a method in accordance with the subject invention. There is a need in the medical and health fields for safe and efficacious skin cancer treatments which are convenient for the patient as well as the health practitioner.